Mortality associated with severe sepsis remains unacceptably high: 30 to 50 percent [Bernard GR, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. New England Journal of Medicine. 2001;344(10):699-709.]. When shock is present, mortality is reported to be even higher: 50 to 60 percent [Friedman G, et al. Has the mortality of septic shock changed with time? Critical Care Medicine. 1998;26(12):2078-2086.].

In addition, the incidence of sepsis is increasing and projected to grow at a rate of 1.5 percent per year [Angus DC, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical Care Medicine. 2001;29(7):1303-1310.]. There are approximately 750,000 new sepsis cases each year, with at least 210,000 fatalities. As medicine becomes more aggressive, with invasive procedures and immunosuppression, the incidence of sepsis is likely to increase even more.

Awareness of the seriousness of this condition remains low; severe sepsis is frequently under-diagnosed at an early stage when it is still potentially reversible. We still see many patients not receiving aggressive therapy early in their course who later are referred to the intensive care unit hours after their initial presentations.

Even though recent trials demonstrate mortality benefit with new interventions (see below), these interventions are still not being applied uniformly or in a timely fashion to the population of patients who need them. Reliability in the care of these patients is low; until standard processes are applied to this problem, best-known care will remain haphazard and unreliable and we will fail to achieve the target goal of significantly reducing mortality.

Severe sepsis and septic shock are areas of medicine and surgery where great strides can be made that can save thousands of lives. In addition, by finding better ways of working together, and new methods of reducing variability and increasing the reliability of our care processes, we will create new practice styles that will ensure that every patient receives the best-known care possible. This effort has the potential to transform the way medicine is practiced, as we learn to build into our routine practice methods of improvement that can be applied to other areas of medicine.

The Problem

1. Inconsistency in the early diagnosis of severe sepsis and septic shock
2. Frequent inadequate volume resuscitation without defined endpoints
3. Late or inadequate use of antibiotics
4. Frequent failure to support the cardiac output when depressed
5. Frequent failure to control hyperglycemia adequately
6. Frequent failure to use low tidal volumes and pressures in acute lung injury
7. Frequent failure to treat adrenal inadequacy in refractory shock

Better Models of Care Exist
Better models of care exist that should be applied more uniformly to all appropriate patients with severe sepsis and septic shock, including the following:

• Early recognition of severe sepsis and septic shock, with early aggressive resuscitation aimed at meeting defined goals [Rivers E, et al. Early recognition of severe sepsis and septic shock, with early aggressive resuscitation aimed at meeting defined goals. New England Journal of Medicine. 2001;345(19):1368-1377.]
• Early use of appropriate antibiotics [Iregui M, et al. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest. 2002;122(1): 262-268.]
• Tight control of blood glucose [van den Berghe G, et al. Intensive insulin therapy in critically ill patients. New England Journal of Medicine. 2001;345(19):1359-1367.]
• Low volume and low pressure ventilation for acute lung injury patients [The NIH-ARDS Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New England Journal of Medicine. 2000;342(18):1301-1308.]
• Use of activated protein C for severe sepsis [Bernard GR, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. New England Journal of Medicine. 2001;344(10): 699-709.]
• Use of low-dose steroids in refractory septic shock [Annane D, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. Journal of the American Medical Association. 2002;288(7):862-887.]